Alcohol use is primarily initiated during vulnerable developmental years when white matter tracts arborize within the prefrontal cortex (PFC), and between the PFC, anterior cingulate, ventral striatum and limbic (affective) structures, and significant synaptic pruning occurs. This neuronal fine-tuning establishes the scaffolding for the progressive neurodevelopment of executive cognitive and emotional regulatory functions that are critical for emotional and behavioral self-control. The vulnerability of this process in adolescence may explain findings of impairments in adolescents with alcohol use problems and in adults with a history of chronic alcohol use that began in adolescence;early alcohol use and heavy episodic drinking in adolescence may lead to long-term neural and behavioral developmental consequences. Also unknown is whether some of the neurodevelopmental delays and deficits associated with alcohol use actually predate use, thereby increasing propensity to misuse alcohol. And as precursor conditions, they may be particularly susceptible to further damage in response to the continued use of alcohol. No study to date has attempted to track neurodevelopmental precursors and the changes in these processes resulting from varying levels of alcohol use throughout adolescence. The proposed 5-year prospective longitudinal fMRI study seeks to identify functional neuroanatomical substrates of neurodevelopmental liability to initiate and escalate alcohol use and chart the progressive nature of neurocognitive change as a consequence of varying levels of alcohol use during adolescence. This study will also, in effect, isolate the potential dose-dependent neurodevelopmental consequences of alcohol use from precursor conditions. Alcohol and drug-"na[unreadable]ve" 11- to 13-year-olds will be prescreened for characteristics predictive of alcohol problems to ensure that a sufficient number of youth (final n=154) will exhibit initiation and varying levels of escalation of drinking during the course of the study. Three 16 month waves of data collection will be conducted. Neurocognitive markers of developmental deficits and delays (e.g., inattention, risky decision making, emotional dysregulation) have been associated with alcohol, tobacco, and other drug use in previous research conducted by the study team and others, thus laying the groundwork for a longitudinal investigation of neurocognitive vulnerability factors in initiation and escalation of alcohol use and its potential effects (e.g., Brown &Tapert, 2004;Fishbein et al., 2005a,b;Giancola et al., 1996;Sher et al., 1997;Tarter et al., 2004;Zeigler et al., 2005). In all analyses, adjustments will be made for concurrent use of tobacco and other drugs, SES, IQ, parental alcohol and drug abuse, and other relevant covariates, such as aggression, alcohol expectancies, normative beliefs about alcohol, social supports, and deviance. Overall, the proposed study has implications for understanding underlying mechanisms in the development of maladaptive social behaviors that increase risk for alcohol initiation and escalation and suggest specific strategies for interventions that strengthen these functions, thereby altering the developmental trajectory for at-risk adolescents. PUBLIC HEALTH RELEVANCE: Alcohol use in adolescence is of particular concern due to the potentially adverse effects of alcohol consumption on neurocognitive functioning during a vulnerable period of development. The proposed fMRI study will comprehensively assess and follow a relatively large cohort of adolescents over a five year period to identify neurodevelopmental precursors of alcohol use initiation and escalation, and subsequent neurocognitive consequences of varying levels of alcohol use, including heavy drinking. Illuminating the risk factors for and effects of alcohol use on the development of neurocognitive skills has implications for designing interventions aimed at developmental cognitive and emotional regulatory processes, especially since such impairments can undermine intervention efforts.